Claims for Patent: 10,213,487

Summary for Patent: 10,213,487

Title:	Nasal powder formulation for treatment of hypoglycemia
Abstract:	The present invention provides a powder formulation containing glucagon or a glucagon analog for nasal administration, useful in the treatment of hypoglycemia, and in particular the treatment of severe hypoglycemia. The present invention also provides a method of making this powder formulation, and to devices and methods for using the powder formulation.
Inventor(s):	Mantripragada; Sankaram (Windsor, CO), Piche; Claude A. (Verdun, CA), Van Betsbrugge; Jo Jan Filip (Laval, CA)
Assignee:	Eli Lilly and Company (Indianapolis, IN)
Application Number:	15/545,332
Patent Claims:	1. A powder composition comprising glucagon (SEQ ID NO: 1), a phospholipid, and -cyclodextrin, wherein the ratio of glucagon to phospholipid to -cyclodextrin is 1:1:8 by weight. 2. The powder composition of claim 1, wherein the phospholipid is at least one member selected from the group consisting of dodecylphosphocholine, didecylphosphatidylcholine, lysolauroylphosphatidylcholine, dioctanoylphosphatidylcholine, dilauroylphosphatidylglycerol or mixtures thereof. 3. The powder composition of claim 2, wherein the phospholipid is dodecylphosphocholine. 4. The powder composition of claim 2, wherein the phospholipid is didecylphosphatidylcholine. 5. The powder composition of claim 2, wherein the phospholipid is lysolauroylphosphatidylcholine. 6. The powder composition of claim 2, wherein the phospholipid is dioctanoylphosphatidylcholine. 7. The powder composition of claim 2, wherein the phospholipid is dilauroylphosphatidylglycerol. 8. A powder composition consisting of glucagon (SEQ ID NO: 1), dodecylphosphocholine, and -cyclodextrin, wherein the ratio of glucagon to dodecylphosphocholine to -cyclodextrin is 1:1:8 by weight. 9. The powder composition according to claim 1, further comprising sodium citrate or citric acid. 10. The powder composition according to claim 9, wherein the amount of sodium citrate or citric acid is up to 10 percent by weight of the overall weight of the composition. 11. The powder composition according to claim 1, further comprising water. 12. The powder composition according to claim 11 wherein the water content of the composition is below 5 percent by weight of the overall weight of the composition. 13. A nasal applicator for a powder formulation, said applicator including a powder formulation reservoir, and a powder formulation contained within the reservoir, wherein the powder formulation is a composition in accordance with claim 1. 14. A method for preparing a powder formulation of claim 1, wherein at least a portion of the powder is present in a phase characterized by an XRPD mesopeak as determined by x-ray powder diffraction, said method comprising the steps of a. forming a first solution of the glucagon (SEQ ID NO. 1) and the phospholipid in an aqueous carrier, wherein the phospholipid is present in a concentration greater than or equal to the critical micelle concentration; b. adding the -cyclodextrin to the first mixture to form a second mixture; c. drying the second mixture to form a solid formulation; and d. processing the solid formulation to produce a uniform powder, said uniform powder including at least a portion of the powder in a phase characterized by an XRPD mesopeak. 15. A method for preparing a powder formulation of claim 1, said method comprising the steps of a. forming a first solution of the glucagon (SEQ ID NO. 1) and the phospholipid in an aqueous carrier, wherein the phospholipid is present in a concentration greater than or equal to the critical micelle concentration; b. adding the -cyclodextrin to the first mixture to form a second mixture; c. drying the second mixture to form a solid formulation; and d. processing the solid formulation to produce a uniform powder. 16. The method of claim 14, wherein the drying of the second mixture is carried out by freeze drying or spray drying the second mixture. 17. The method of claim 15, wherein the drying of the second mixture is carried out by freeze drying or spray drying the second mixture. 18. A method for treating hypoglycemia in an individual suffering from hypoglycemia comprising administering to the individual a composition in accordance with claim 1, wherein the composition is administered in a therapeutically effective amount as a powder to the nasal mucosa of the individual. 19. The method of claim 18, wherein the powder formulation is administered to only one nostril of the individual.